Flinn Highlights CAR T-Cell Developments in Lymphoma

With several approvals this past year, chimeric antigen receptor (CAR) T-cell therapy is becoming a significant part of treatment for select patients with hematologic malignancies.

Tisagenlecleucel (Kymriah) was approved by the FDA in May 2018 for adult patients with relapsed/refractory large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma, after 2 or more lines of systemic therapy. The approval was based on findings from the phase II JULIET study, updated data of which showed an overall response rate (ORR) of 52%, with a complete response (CR) rate of 40%.1

Previously, the FDA approved the CAR T-cell therapy axicabtagene ciloleucel (axi-cel; Yescarta) in October 2017 as a treatment for adults with relapsed/refractory non-Hodgkin lymphoma (NHL). The decision was based on findings from the single-arm ZUMA-1 study, in which axi-cel demonstrated an ORR of 82% and a CR rate of 54%. After 8.7 months of follow-up, 39% of patients remained in CR.2

Longer follow-up presented at the 2018 ASCO Annual Meeting showed that, at a median follow-up of 15.4 months, the ORR was 82% and the CR rate increased to 58%.3

According to Ian W. Flinn, MD, PhD, this new avenue of treatment has brought hope to doctors and patients alike, but there is still a long way to go before it becomes part of frontline therapy.

In an interview during the 2018 OncLive® State of the Science Summit™, A Summer of Progress: Updates from ASCO 2018, Flinn, director of lymphoma research, principal investigator, Sarah Cannon Research Institute, discussed the latest developments with CAR T-cell therapies and other recent advances in the field of lymphoma.

OncLive: Can you provide some background to your presentation on lymphoma?

Flinn: I spoke about a number of different presentations that have occurred over the last 6 months, at the 2018 ASCO Annual Meeting and other meetings, looking at advances in both Hodgkin lymphoma and NHL, including small molecule inhibitors, chemotherapy, and CAR T-cell therapy.

What are some key updates from these recent data?

In follicular lymphoma, one of the key updates is the RELEVANCE study that compared rituximab (Rituxan) and chemotherapy with rituximab and lenalidomide (Revlimid; R2). This study was a large, international trial. It was based on some phase II data that suggested the R2 regimen, rituximab plus lenalidomide, had very high remission rates and very tolerable toxicity. Therefore, that was an exciting phase II study that led to this randomized trial.

In this randomized trial—while technically it did not meet its primary endpoint, which was superiority of the R2 regimen to chemotherapy—the response rates and progression-free survival between the 2 treatments was nearly identical. This is interesting because it offers a nonchemotherapy approach to frontline treatment of [patients with] follicular lymphoma. I suspect that some patients and their doctors will want to use this approach to avoid the toxicity that we normally see with rituximab and chemotherapy.

Other updates included CAR T cells from the JULIET and ZUMA-1 trials. The ZUMA-1 trial is a study of CD19-targeted CAR T-cells. This was previously published in the New England Journal of Medicine and now we see response rates in this update. The interesting thing that we saw here was the durability of the remission.

It turns out that if people achieve a full or partial response, and if they keep that remission for 3 months, they are very likely to maintain that for a long time. This was a great update for us as we continue to learn more about CAR T cells.

The JULIET trial involves the competing product [axicabtagene ciloleucel] that was just FDA approved for relapsed/refractory large cell lymphoma. Again, it's a CD19-targeted CAR T-cell product. As difficult as it as to compare the trials, a lot of people want to compare them. However, they are both very exciting. It involved 2 very different patient populations.